Action Points

This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Note that this dose-escalation study of six women with 21-hydroxylase deficiency demonstrated that the addition of abiraterone to standard therapy resulted in reduction of androgens without hyperkalemia or hypertension.

Be aware that larger studies will be needed to confirm this efficacy profile and the use of abiraterone for this indication remains off-label.

In a small but much talked about proof-of-concept study, mean serum androstenedione normalized in five of six patients with congenital adrenal hyperplasia, falling from a median baseline of 664 ng/dL to 126 ng/dL after 7 days, Richard Auchus, MD, of the University of Michigan in Ann Arbor, and colleagues reported during a late-breaking session at the Endocrine Society meeting.

"I think we can conclude from these data that abiraterone (Zytiga) at 250 mg with hydrocortisone 20 mg per day for 1 week normalizes androgens in the majority of adult women with classic 21-hydroxylase deficiency without causing hypertension or hypokalemia," Auchus said during the session.

Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center in New York City and co-chair of this year's meeting, told MedPage Today that even though they're from a very small trial, the findings are impressive and could have immediate clinical implications, with a high likelihood of off-label use.

"I think it's very seldom that you see clinicians start using things like this [based on results from] just five or six patients, but it will happen with this drug," Tuttle said.

"It's one of those observations that opens the door," he continued. "Every once in a while in medicine, you get the opportunity to have a new way to treat something. And what this allows us to do is to replace glucocorticoids and aldosterone just at normal levels, and use the new drug to block testosterone synthesis."

Patients with 21-hydroxylase deficiency are currently treated with high doses of glucocorticoids, but this can lead to Cushing's disease-like symptoms.

They conducted an open-label, proof-of-concept, dose-finding trial in six adult women with classic 21-hydroxylase deficiency. Median patient age was 36 and the median body mass index (BMI) was 36.7 kg/m2.

The primary endpoint was normalization of mean androstenedione levels in at least 80% of patients within 6 to 7 days of treatment. Secondary endpoints included levels of testosterone and urine androgens.

The researchers conducted dose escalation of abiraterone from 100 mg/day to 250 mg/day over 6 days, which was continued until at least 80% of patients had a normalization of androstenedione.

Overall, they found that at a dose of 100 mg/day, mean serum androstenedione levels normalized in 50% of patients, with a reduction from a median baseline level of 764 ng/dL to a median level of 245 ng/dL by the end of the trial.

The primary endpoint was met at 250 mg/day with mean androstenedione levels normalizing in five of six patients, with a decrease from a median baseline of 664 ng/dL to 126 ng/dL by the end of the study, the researchers reported.

Serum testosterone and urine testosterone metabolites fell in parallel to the changes in androstenedione, they added, and the drug was safe and well tolerated with no adverse events of hypertension of hypokalemia, which are concerns with higher doses of the drug when used in prostate cancer.

The study was limited because it only looked at adult females taking oral contraceptives and who had only classic 21-hydroxylase deficiency. It was also limited by its short duration of therapy and by the small number of participants included.

Still, Auchus and colleagues concluded that abiraterone at 250 mg/day with hydrocortisone 20 mg/day for a week "normalizes androgens in the majority of adult women with classic 21-hydroxylase deficiency, without causing hypertension or hypokalemia."

Tuttle said the findings will likely "open a whole new field for how we replace these 21-hydroxylase patients."

However, meeting co-chair Diane Robins, PhD, of the University of Michigan in Ann Arbor, called the work "promising" but with the caveat that it was still "too soon to tell if it's game-changing."

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